1. Amat AZ, Zhao H, Swanson A, Weitlauf AS, Warren Z, Sarkar N. Design of an Interactive Virtual Reality System, InViRS, for Joint Attention Practice in Autistic Children. IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society. 2021; 29: 1866-76.

Many children with Autism Spectrum Disorder (ASD) exhibit atypical gaze behaviors related to joint attention, a fundamental social-communication skill. Specifically, children with ASD show differences in the skills of gaze sharing and gaze following. In this work we present a novel virtual reality (VR)-based system, called InViRS, in which children with ASD play games allowing them to practice gaze sharing and gaze following. InViRS has three main design contributions: (i) a closed-loop joint attention paradigm with real-time tracking of the participant’s eye gaze and game performance measures, (ii) an assistive feedback mechanism that provides guidance and hints in real time, and (iii) a controller that adaptively changes the avatar’s gaze prompts according to the performance measures. Results from a pilot study to evaluate the feasibility of InViRS with 9 autistic(1) children and 9 typically developing (TD) children offered preliminary support for the feasibility of successful gameplay as well as positive impacts on the targeted skills of gaze sharing and gaze following.

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2. Arkesteyn A, Van Damme T, Thoen A, Cornelissen V, Healy S, Vancampfort D. Physical activity correlates in children and adolescents with autism spectrum disorder: a systematic review. Disability and rehabilitation. 2021: 1-12.

PURPOSE: This systematic review examined correlates of physical activity (PA) at all levels of the socio-ecological model (i.e., intrapersonal, interpersonal, environmental and policy level) in children and adolescents with autism spectrum disorder (ASD). MATERIALS AND METHODS: Major electronic databases were searched from inception until March 23(rd), 2021. A summary coding was used to analyze the data for children (3-12 years) and adolescents (13-18 years) with ASD separately. RESULTS: Out of the 79 potential PA correlates, retrieved from 32 studies (991 657 children; 3857 adolescents), only five correlates were consistently examined as a PA correlate (i.e., examined in four or more studies) in children and adolescents with ASD. Only age was inversely associated with PA in children and adolescents with ASD. Data on gender, body mass index, autism severity level and day of the week being physically active in children with ASD were mixed. CONCLUSIONS: We only found consistent evidence for age being inversely related to PA. Our review indicates that more research is needed to explore intrapersonal, interpersonal, environmental and policy-related correlates of PA in children and adolescents with ASD.IMPLICATIONS FOR REHABILITATIONRehabilitation programs should take into account that in particular older children and adolescents with autism spectrum disorder are at risk for physical inactivity.Boys and girls with autism spectrum disorder need the same care when motivating them to be more physically active.

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3. Cetinoglu E, Aras S. The Autism-Spectrum Quotient (AQ) Adolescent’s Version in Turkey: Factor Structure, Reliability and Validity. Journal of autism and developmental disorders. 2021.

We assessed the reliability and validity of the Turkish version of the autism spectrum quotient (AQ)-adolescent. Three assessment groups of adolescents, aged 11-18, were: 80 with Asperger syndrome/high-functioning autism (AS/HFA), 71 with other psychiatric disorders (PDs; 35 major depression, 18 obsessive-compulsive disorder, 18 social phobia), and 249 healthy controls. The scores of the AS/HFA group were significantly higher than the healthy control and PD groups. Cronbach α value was 0.829. Ordinal alpha value was 0.90. We showed the AQ-adolescent four-factor structure in the factor analysis. In the test-retest of AQ-adolescent and subscale scores, « very strong » significant correlation values were detected. A cut-off score of 24 best distinguished the autism group from healthy controls with 0.975 sensitivity and 0.991 specificity.

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4. Fontana P, Ginevrino M, Bejo K, Cantalupo G, Ciavarella M, Lombardi C, Maioli M, Scarano F, Costabile C, Novelli A, Lonardo F. A ZFHX4 mutation associated with a recognizable neuropsychological and facial phenotype. European journal of medical genetics. 2021; 64(11): 104321.

Several patients with chromosomal deletions including ZFHX4 gene have been described, whereas point mutations are very rare. This gene encodes for a transcription factor involved in the development of several embryonal processes, including brain differentiation. Patients with 8q21.11 deletions usually show intellectual disability, short stature, peculiar facial features, and severe eye abnormalities. We describe a female patient with mild intellectual disability, autism spectrum disorder, strabismus, ptosis, low-set and prominent ears, high-arched palate, microretrognathia. Clinical Exome Sequencing revealed the presence of a de novo heterozygous variant in ZFHX4. Therefore, we further investigate the different phenotypes of ZFHX4 mutations and 8q21.11 deletions.

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5. Guevara-Gonzaléz J, Guevara-Campos J, González L, Cauli O. The Effects of Probiotics and Prebiotics on Gastrointestinal and Behavioural Symptoms in Autism Spectrum Disorder. Current reviews in clinical and experimental pharmacology. 2022; 17(3): 166-73.

BACKGROUND: Autism Spectrum Disorders (ASDs) are a group of prevalent neuropsychiatric disorders. They present a complex and unknown etiology, which in most cases includes significant peripheral alterations outside the brain such as in the composition of gut microbiota. Because the gut microbiota is involved in modulating the gut-brain axis, several studies have suggested that the microbiome in the gut can modify metabolites which are able to cross the blood-brain barrier and modulate brain function. METHODS: We reviewed the current evidence regarding microbiota alterations in patients with ASD and the effects of the administration of probiotics and prebiotics in these patients, both in terms of gastrointestinal and behavioural symptoms. RESULTS: Administration of a probiotic formulation containing different strains of Lactobacillus (L. acidophilus, L. rhamnosus, and others) and Bifidobacteria had beneficial effects upon these aforementioned symptoms and their use is recommended in a subgroup of ASD patients that present gastrointestinal disturbances. Nonetheless, the types of gastrointestinal disturbances that most benefit from such interventions remain to be elucidated in order to personalize the medical approaches. CONCLUSION: Recent clinical studies have shown that probiotic treatments can regulate the gut microbiota and may result in improvements in some behavioral abnormalities associated with ASD. Trials using prebiotic fibers or synbiotics preparations are still lacking and necessary in order to deep in such therapeutic strategies in ASD with comorbid gastrointestinal disrturbances.

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6. Krämer K, Vetter A, Schultz-Venrath U, Vogeley K, Reul S. Mentalization-Based Treatment in Groups for Adults With Autism Spectrum Disorder. Frontiers in psychology. 2021; 12: 708557.

In order to successfully interact with others in social encounters, we have to be attentive to their mental states. This means, we have to implicitly and explicitly interpret our own actions as well as the actions of others as meaningful on the basis of the ascription of intentional mental states. However, this ability, often referred to as mentalizing, seems to be impaired in autism spectrum disorder (ASD). Individuals with ADS show specific deficits relating to the representation of mental states of others. Especially, the spontaneous, intuitive attribution of and reaction to others’ mental states seem to be impaired. Mentalization-Based Treatment (MBT) is a form of psychotherapy in individual and group settings that focuses on the education and enhancement of mentalizing. Although the scope of MBT is broad and MBT has been already proven to be useful in a variety of mental disorders, no attempt has been made to apply MBT in patients with ASD. In our study, we adapted MBT for adults with ASD in a therapeutic group setting to examine the feasibility as well as the effectiveness of the treatment in this patient group. During 15-20 weeks of weekly group therapy, we surveyed the patients’ acceptability of the intervention. Additionally, changes in mentalizing difficulties were measured before and after treatment. Results show a high acceptance of the treatment and an improvement in the patients’ mentalizing abilities, presenting MBT as a promising treatment option for ASD.

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7. Lafage R, Smith JS, Elysee J, Passias P, Bess S, Klineberg E, Kim HJ, Shaffrey C, Burton D, Hostin R, Mundis G, Ames C, Schwab F, Lafage V. Sagittal age-adjusted score (SAAS) for adult spinal deformity (ASD) more effectively predicts surgical outcomes and proximal junctional kyphosis than previous classifications. Spine deformity. 2022; 10(1): 121-31.

BACKGROUND: Several methodologies have been proposed to determine ideal ASD sagittal spinopelvic alignment (SRS-Schwab classification) global alignment and proportion (GAP) score, patient age-adjusted alignment). A recent study revealed the ability and limitations of these methodologies to predict PJK. The aim of the study was to develop a new approach, inspired by SRS classification, GAP score, and age-alignment to improve the evaluation of the sagittal plane. METHOD: A multi-center ASD database was retrospectively evaluated for surgically treated ASD patients with complete fusion of the lumbar spine, and minimum 2 year follow-up. The Sagittal age-adjusted score (SAAS) methodology was created by assigning numerical values to the difference between each patient’s postoperative sagittal alignment and ideal alignment defined by previously reported age generational norms for PI-LL, PT, and TPA. Postoperative HRQOL and PJK severity between each SAAS categories were evaluated. RESULTS: 409 of 667 (61.3%) patients meeting inclusion criteria were evaluated. At 2 year SAAS score showed that 27.0% of the patients were under-corrected, 51.7% over-corrected, and 21.3% matched their age-adjusted target. SAAS score increased as PJK worsened (from SAAS = 0.2 for no-PJK, to 4.0 for PJF, p < 0.001). Post-operatively, HRQOL differences between SAAS groups included ODI, SRS pain, and SRS total. CONCLUSION: Inspired by SRS classification, the concept of the GAP score, and age-adjusted alignment targets, the results demonstrated significant association with PJK and patient reported outcomes. With a lower rate of failure and better HRQOL, the SAAS seems to represent a "sweet spot" to optimize HRQOL while mitigating the risk of mechanical complications.

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8. Luhach K, Kulkarni GT, Singh VP, Sharma B. Cilostazol attenuated prenatal valproic acid-induced behavioural and biochemical deficits in a rat model of autism spectrum disorder. The Journal of pharmacy and pharmacology. 2021; 73(11): 1460-9.

OBJECTIVES: Autism spectrum disorder (ASD) is categorized as a neurodevelopmental disorder, presenting with a variety of aetiological and phenotypical features. Inhibiting the enzyme phosphodiesterase-3 (PDE3) with cilostazol is known to produce beneficial effects in several brain disorders. The pharmacological outcome of cilostazol administration was investigated in prenatal valproic acid (VPA)-induced ASD deficits in albino Wistar rats. METHODS: Cilostazol was administered in two doses (30/60 mg/kg) to male rats born of females administered with VPA on gestational day 12. Behavioural assays on locomotion (open field), social interaction, repetitive behaviour (y-maze) and anxiety (elevated plus maze) were performed in all groups. Further, biochemical assessments of markers associated with neuronal function (BDNF, pCREB), inflammation (TNF-α, IL-6, IL-10) and oxidative stress were carried out in frontal cortex, hippocampus, striatum and cerebellum. KEY FINDINGS: The cilostazol regimen, attenuated prenatal VPA exposure associated hyperlocomotion, social interaction deficits, repetitive behavior, and anxiety. Further, biochemical markers such as BDNF, pCREB, IL-10 and GSH were found to be significantly increased contrary to markers such as TNF-α, IL-6 and TBARS in the assessed brain regions. CONCLUSIONS: Cilostazol rectified core behavioural traits while producing significant changes to biochemistry in the brain, suggesting benefits of cilostazol administration in experimental models of ASD.

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9. Manohar H, Kandasamy P. Clinical outcomes of children with ASD – Preliminary findings from a 18 month follow up study. Asian journal of psychiatry. 2021; 64: 102816.

BACKGROUND: Parent-mediated intervention for children with Autism Spectrum Disorder (ASD) is a critical component to deliver evidence-based interventions in resource-limited settings. There is a need for methodologically rigorous longitudinal and follow-up studies of children with ASD to understand clinical outcome and developmental trajectories. METHODS: We report the clinical outcome at 18-month follow-up of children diagnosed with ASD who received parent-mediated intervention for a 3-month period as part of a feasibility study. The study participants were followed up for 18 months as part of Treatment As Usual (TAU). Symptom severity and adaptive functioning were assessed on Childhood Autism Rating Scale (CARS) and Vineland Social Maturity Scale (VSMS) respectively. RESULTS: All the study participants(n = 42), continued to show improvement between baseline and the two follow-up evaluations at 3 months and 18 months respectively, with reduction in symptom severity, improvement in core features of ASD and adaptive functioning. The maximum gains were attained during the first three months. Three subgroups were identified based on the trajectory of improvement: 1) Children with best possible outcomes, 2) Child with maintenance of gains, and 3) Children with minimal improvement. Seven participants (16.7 %) had the ‘best possible’ outcome at 18-month follow-up with CARS scores in the non-autistic range and they no longer qualified for a DSM-5 diagnosis of ASD. CONCLUSION: The intensity of early intervention is pivotal to positively alter the developmental trajectories in children with ASD. Parent-mediated intervention is the best possible mode of intervention delivery to initiate early intervention and address the prevailing challenges in resource-limited settings.

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10. Matsui T, Uchida M, Fujino H, Tojo Y, Hakarino K. Perception of native and non-native phonemic contrasts in children with autistic spectrum disorder: effects of speaker variability. Clinical linguistics & phonetics. 2021: 1-19.

The current study investigated speech perception in children with ASD by directly comparing discrimination accuracy of phonemic contrasts in the native and non-native languages. The effect of speaker variability on phoneme perception was also examined. We also explored the relation between language impairment and accuracy in phoneme discrimination in children with ASD. Significant differences in performance were found between the ASD and TD groups on discrimination of the native phonemic contrasts. By contrast, no difference was found between the two groups on discrimination of the non-native phonemic contrasts. Further subgroup analysis revealed that the ALN group (ASD without language delay or impairment) showed significantly higher discrimination accuracy for the native syllable contrasts than the non-native counterpart. No significant difference was found in the discrimination accuracy between the native and non-native phonemic contrasts in the ALD group (ASD with language delay or impairment). The effect of speaker viability on phoneme discrimination was observed in the TD group but not in the ASD subgroups. Nonverbal reasoning ability was highly related to discrimination accuracy of both the native and non-native phonemic contrasts in children with ASD. The results of the present study suggest that speech perception in children with ASD is not as attuned to their native language as in their TD peers. Our findings also indicate that language delay or impairment is related to difficulty in perception of native phonemes in children with ASD.

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11. Moseley RL, Liu CH, Gregory NJ, Smith P, Baron-Cohen S, Sui J. Levels of Self-representation and Their Sociocognitive Correlates in Late-Diagnosed Autistic Adults. Journal of autism and developmental disorders. 2021.

The cognitive representation of oneself is central to other sociocognitive processes, including relations with others. It is reflected in faster, more accurate processing of self-relevant information, a « self-prioritisation effect » (SPE) which is inconsistent across studies in autism. Across two tasks with autistic and non-autistic participants, we explored the SPE and its relationship to autistic traits, mentalizing ability and loneliness. A SPE was intact in both groups, but together the two tasks suggested a reduced tendency of late-diagnosed autistic participants to differentiate between familiar and unfamiliar others and greater ease disengaging from the self-concept. Correlations too revealed a complex picture, which we attempt to explore and disentangle with reference to the inconsistency across self-processing studies in autism, highlighting implications for future research.

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12. Pennisi P, Giallongo L, Milintenda G, Cannarozzo M. Correction to: Autism, autistic traits and creativity: a systematic review and meta-analysis. Cognitive processing. 2021; 22(4): 733.

In the original publication of the article, the first and last names of the authors are interchanged and published incorrectly. The correct author names are given below: Paola Pennisi, Laura Giallongo, Giusy Milintenda, Michela Cannarozzo.

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13. Sewell R, Buchanan CL, Davis S, Christakis DA, Dempsey A, Furniss A, Kazak AE, Kerlek AJ, Magnusen B, Pajor NM, Pyle L, Pyle LC, Razzaghi H, Schwartz BI, Vogiatzi MG, Nokoff NJ. Behavioral Health Diagnoses in Youth with Differences of Sex Development or Congenital Adrenal Hyperplasia Compared with Controls: A PEDSnet Study. The Journal of pediatrics. 2021; 239: 175-81.e2.

OBJECTIVE: To evaluate the odds of a behavioral health diagnosis among youth with differences of sex development (DSD) or congenital adrenal hyperplasia (CAH) compared with matched controls in the PEDSnet database. STUDY DESIGN: All youth with a diagnosis of DSD (n = 1216) or CAH (n = 1647) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables (1:4) with controls (n = 4864 and 6588, respectively) using multivariable logistic regression. The likelihood of having behavioral health diagnoses was examined using generalized estimating equations. RESULTS: Youth with DSD had higher odds of a behavioral health diagnosis (OR, 1.7; 95% CI, 1.4-2.1; P < .0001) and neurodevelopmental diagnosis (OR, 1.7; 95% CI, 1.4, 2.0; P < .0001) compared with matched controls. Youth with CAH did not have an increased odds of a behavioral health diagnosis (OR, 1.0; 95% CI, 0.9, 1.1; P = .9) compared with matched controls but did have higher odds of developmental delay (OR, 1.8; 95% CI, 1.4, 2.4; P < .0001). CONCLUSIONS: Youth with DSD diagnosis have higher odds of a behavioral health or neurodevelopmental diagnosis compared with matched controls. Youth with CAH have higher odds of developmental delay, highlighting the need for screening in both groups.

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14. Wandin H, Lindberg P, Sonnander K. Aided language modelling, responsive communication and eye-gaze technology as communication intervention for adults with Rett syndrome: three experimental single case studies. Disability and rehabilitation Assistive technology. 2021: 1-15.

PURPOSE: To examine the effect of a communication intervention package on expressive communication and visual attention in individuals with Rett syndrome. MATERIALS AND METHODS: A modified withdrawal (A-B1-A1-B2-A2) single case experimental design with a direct inter-subject replication across three participants was applied. Three women with Rett syndrome participated. The study took place over a six-week period and comprised 32 sessions with each participant. All sessions were video recorded. During the intervention the communication partner used aided language modelling on a gaze-controlled device in combination with using responsive partner strategies. Expressive communication was assessed as synthesised words per minute and unique synthesised words per minute. Visual attention was assessed as rate of focused gazes (1 s or longer) in interaction. RESULTS: An intervention effect was found on the rate of unique words for all participants. The rate of words increased for two participants when the intervention was introduced but no withdrawal effect could be seen. An intervention effect on visual attention could be seen for one participant. The intervention appeared to have social validity as reported by caregivers. CONCLUSION: Aided language modelling (ALM), while using responsive partner strategies and a gaze-controlled device may be used with adult individuals with Rett syndrome to increase their rate of expressive communication. Detailed observational measures revealed individual learning patterns, which may provide clinically valuable insights.Implications for RehabilitationAdults with Rett syndrome may benefit from access to gaze-controlled devices in combination with responsive partner strategies.Responsive partner communication may be effective for some individuals with Rett syndrome to increase their rate of synthesised utterances.Rate of focused gazes may be considered as an outcome measure for individuals with oculomotor difficulties when introducing aided language modelling.

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15. Wang X, Xu M, Xu Q, Yang F, Tang H, Shao C, Wang L, Wang Y, Deng J, Wang S. Rictor is involved in Ctnnd2 deletion-induced impairment of spatial learning and memory but not autism-like behaviors. Frontiers in bioscience (Landmark edition). 2021; 26(8): 335-46.

Background: The CTNND2 gene which encodes a δ-catenin protein (CTNND2) is associated with multiple severe neurological disorders. However, the specific role of CTNND2 in spatial cognition and related mechanisms remains obscure. Methods: In this study, we generated a new line of Ctnnd2-Knock out (KO) mice with its exon2 deleted, and then characterized their behavioral phenotypes and explore the Biological mechanism. Results: Ctnnd2-KO mice were with typical autism-like behaviors as evidenced by reduced social interaction in three-chamber sociability test, more frequent stereotypic behaviors (self-grooming), and deficits in spatial learning and memory tested by the Morris water maze. Furthermore, the expression of Rictor protein, a core component of the mTORC2 complex, was significantly decreased in the hippocampus of mutant mice. ShRNA-induced knockdown of Rictor protein in the hippocampus of both Ctnnd2-KO mice and wild-type mice exacerbated spatial learning and memory deficits but did not affect their autism-like behaviors. Mechanistically, the hippocampal CA1 neurons of Ctnnd2-KO mice showed decreased actin polymerization, postsynaptic spine density. Down-regulation of Rictor resulted in altered expression of post-synaptic proteins such as GluR1 and ELKS, but not presynaptic protein Synapsin1, implying abnormal synaptic changes in KO mice. Conclusion: The CTNND2 gene is involved in spatial learning and memory via Rictor-mediated actin polymerization and synaptic plasticity. Our study provides a novel insight into the role and mechanisms of the Ctnnd2 gene in cognition at the molecular and synaptic levels.

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16. Wood JJ, Kuhfeld M, Sturm A, Cai L, Wood KS, Cornejo Guevara MV, Galán CA, Johnson AR, Cho AC, Weisz JR. Personalized autism symptom assessment with the Youth Top Problems Scale: Observational and parent-report formats for clinical trials applications. Psychological assessment. 2022; 34(1): 43-57.

Few measures of autism-related symptoms have been established as both psychometrically robust and sensitive to the effects of treatment. In the present study, a personalized measure of autism-related symptoms using the Youth Top Problems (YTP) method (Weisz et al., 2011) was evaluated. Participants included 68 children with diagnoses of autism (ages 6-13 years), and their parents, who were randomized to cognitive behavioral therapy (CBT) or enhanced standard community treatment (ESCT) addressing autism-related symptoms. At pretreatment, parents described their child’s top autism-related problems (YTPs) in their own words and rated the severity of these problems on a Likert-type scale. Parents also made daily severity ratings on the child’s top three YTPs for 5 days prior to treatment and 5 days following treatment while videorecording their child’s behavior at home on each of these days. Trained observers coded these videorecordings, focusing on the same YTPs that the parents rated. Parents also completed standardized checklists of autism-related symptoms and general mental health symptoms. There was evidence of convergent and discriminant validity as well as good test-retest reliability for the YTP measures. YTP severity scores converged with the standardized measure of autism-related symptoms. Parent-reported YTP scores predicted observers’ YTP scores at the daily level, and both parent-reported and observers’ YTP scores decreased from pre- to post treatment. Observers’ ratings of the videorecordings exhibited sensitivity to treatment condition. These applications of the YTP method are promising and may complement standardized symptom checklists for clinical trials focusing on autism-related symptoms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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17. Zhao J, Zhang Z, Wan L, Li X, Kang J. [Electroencephalogram feature extraction and classification of autistic children based on recurrence quantification analysis]. Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi. 2021; 38(4): 663-70.

Extraction and analysis of electroencephalogram (EEG) signal characteristics of patients with autism spectrum disorder (ASD) is of great significance for the diagnosis and treatment of the disease. Based on recurrence quantitative analysis (RQA)method, this study explored the differences in the nonlinear characteristics of EEG signals between ASD children and children with typical development (TD). In the experiment, RQA method was used to extract nonlinear features such as recurrence rate (RR), determinism (DET) and length of average diagonal line (LADL) of EEG signals in different brain regions of subjects, and support vector machine was combined to classify children with ASD and TD. The research results show that for the whole brain area (including parietal lobe, frontal lobe, occipital lobe and temporal lobe), when the three feature combinations of RR, DET and LADL are selected, the maximum classification accuracy rate is 84%, the sensitivity is 76%, the specificity is 92%, and the corresponding area under the curve (AUC) value is 0.875. For parietal lobe and frontal lobe (including parietal lobe, frontal lobe), when the three features of RR, DET and LADL are combined, the maximum classification accuracy rate is 82%, the sensitivity is 72%, and the specificity is 92%, which corresponds to an AUC value of 0.781. The research in this paper shows that the nonlinear characteristics of EEG signals extracted based on RQA method can become an objective indicator to distinguish children with ASD and TD, and combined with machine learning methods, the method can provide auxiliary evaluation indicators for clinical diagnosis. At the same time, the difference in the nonlinear characteristics of EEG signals between ASD children and TD children is statistically significant in the parietal-frontal lobe. This study analyzes the clinical characteristics of children with ASD based on the functions of the brain regions, and provides help for future diagnosis and treatment.

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